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1.
Cell Death Differ ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594443

RESUMO

Cyclic GMP-AMP synthase (cGAS) is a key innate immune sensor that recognizes cytosolic DNA to induce immune responses against invading pathogens. The role of cGAS is conventionally recognized as a nucleotidyltransferase to catalyze the synthesis of cGAMP upon recognition of cytosolic DNA, which leads to the activation of STING and production of type I/III interferon to fight against the pathogen. However, given that hepatocytes are lack of functional STING expression, it is intriguing to define the role of cGAS in hepatocellular carcinoma (HCC), the liver parenchymal cells derived malignancy. In this study, we revealed that cGAS was significantly downregulated in clinical HCC tissues, and its dysregulation contributed to the progression of HCC. We further identified cGAS as an immune tyrosine inhibitory motif (ITIM) containing protein, and demonstrated that cGAS inhibited the progression of HCC and increased the response of HCC to sorafenib treatment by suppressing PI3K/AKT/mTORC1 pathway in cellular and animal models. Mechanistically, cGAS recruits SH2-containing tyrosine phosphatase 1 (SHP1) via ITIM, and dephosphorylates p85 in phosphatidylinositol 3-kinase (PI3K), which leads to the suppression of AKT-mTORC1 pathway. Thus, cGAS is identified as a novel tumor suppressor in HCC via its function independent of its conventional role as cGAMP synthase, which indicates a novel therapeutic strategy for advanced HCC by modulating cGAS signaling.

2.
Foods ; 13(8)2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38672816

RESUMO

A novel storage technique that combines the low-frequency electric field (LFEF) and ice temperature was used to extend the shelf life of Pacific white shrimp (Penaeus vannamei). The study investigated the effect of LFEF treatment on the quality and microbial composition of Penaeus vannamei during storage at ice temperature. The results showed that the LFEF treatment significantly extended the shelf life of shrimp during storage at ice temperature. The total volatile base nitrogen (TVB-N) and pH of samples increased over time, while the total viable count (TVC) showed a trend of first decreasing and then increasing. Obviously, shrimp samples treated with LFEF had a lower pH, TVB-N and TVC values than the untreated samples (p < 0.05) at the middle and late stages of storage. LFEF treatment increased the diversity and altered the composition of the microbial communities in Penaeus vannamei. Additionally, the treatment led to a decrease in the relative abundance of dominant spoilage bacteria, including Aliivibrio, Photobacterium and Moritella, in Penaeus vannamei stored at ice temperature for 11 days. Furthermore, correlation analysis indicated that TVB-N and pH had a significant and positive correlation with Pseudoalteromonas, suggesting that Pseudoalteromonas had a greater impact on shrimp quality. This study supports the practical application of accelerated low-frequency electric field-assisted shrimp preservation as an effective means of maintaining shrimp meat quality.

3.
Cell Commun Signal ; 22(1): 86, 2024 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291436

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver diseases and has emerged as the leading factor in the pathogenesis of hepatocellular carcinoma (HCC). MyD88 contributes to the development of HCC. However, the underlying mechanism by which MyD88 in myofibroblasts regulates NAFLD-associated liver cancer development remains unknown. RESULTS: Myofibroblast MyD88-deficient (SMAMyD88-/-) mice were protected from diet-induced obesity and developed fewer and smaller liver tumors. MyD88 deficiency in myofibroblasts attenuated macrophage M2 polarization and fat accumulation in HCC tissues. Mechanistically, MyD88 signaling in myofibroblasts enhanced CCL9 secretion, thereby promoting macrophage M2 polarization. This process may depend on the CCR1 receptor and STAT6/ PPARß pathway. Furthermore, liver tumor growth was attenuated in mice treated with a CCR1 inhibitor. CCLl5 (homologous protein CCL9 in humans) expression was increased in myofibroblasts of HCC and was associated with shorter survival of patients with HCC. Thus, our results indicate that MyD88 in myofibroblasts promotes NAFLD-related HCC progression and may be a promising therapeutic target for HCC treatment. CONCLUSION: This study demonstrates that MyD88 in myofibroblasts can promote nonalcoholic fatty liver disease-related hepatocarcinogenesis by enhancing macrophage M2 polarization, which might provide a potential molecular therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Animais , Humanos , Camundongos , Carcinogênese/patologia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Macrófagos/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Miofibroblastos/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo
4.
Theor Appl Genet ; 137(1): 2, 2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-38072878

RESUMO

KEY MESSAGE: Two wheat-Ae. longissima translocation chromosomes (1BS·1SlL and 1SlS·1BL) were transferred into three commercial wheat varieties, and the new advanced lines showed improved bread-making quality compared to their recurrent parents. Aegilops longissima chromosome 1Sl encodes specific types of gluten subunits that may positively affect wheat bread-making quality. The most effective method of introducing 1Sl chromosomal fragments containing the target genes into wheat is chromosome translocation. Here, a wheat-Ae. longissima 1BS·1SlL translocation line was developed using molecular marker-assisted chromosome engineering. Two types of translocation chromosomes developed in a previous study, 1BS·1SlL and 1SlS·1BL, were introduced into three commercial wheat varieties (Ningchun4, Ningchun50, and Westonia) via backcrossing with marker-assisted selection. Advanced translocation lines were confirmed through chromosome in situ hybridization and genotyping by target sequencing using the wheat 40 K system. Bread-making quality was found to be improved in the two types of advanced translocation lines compared to the corresponding recurrent parents. Furthermore, 1SlS·1BL translocation lines displayed better bread-making quality than 1BS·1SlL translocation lines in each genetic background. Further analysis revealed that high molecular weight glutenin subunit (HMW-GS) contents and expression levels of genes encoding low molecular weight glutenin subunits (LMW-GSs) were increased in 1SlS·1BL translocation lines. Gliadin and gluten-related transcription factors were also upregulated in the grains of the two types of advanced translocation lines compared to the recurrent parents. This study clarifies the impacts of specific glutenin subunits on bread-making quality and provides novel germplasm resources for further improvement of wheat quality through molecular breeding.


Assuntos
Aegilops , Triticum , Humanos , Triticum/genética , Triticum/metabolismo , Aegilops/genética , Aegilops/metabolismo , Translocação Genética , Pão/análise , Cromossomos Humanos Par 1/metabolismo , Glutens/genética , Glutens/metabolismo
5.
Int J Biol Macromol ; 253(Pt 3): 126815, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37690646

RESUMO

The relationship between myosin denaturation, aggregation and water migration in Nemipterus virgatus myosin gels with different treatment processes under optimal low pressure coupled with heat treatment was investigated to clarify the molecular mechanism of water migration. With the different treatment processes, the proportion of bound water of the myosin gels increased significantly (P < 0.05). Denaturation of myosin S1 sub-fragments and α-helical unfolding during different treatment processes led to an increase in ß-sheets content. These promote increased exposure of Try residues and hydrophobic groups of myosin, formation of clathrate hydrates, and reduced mobility of bound water. Furthermore, hydrophobic interactions and disulfide bonds caused the head-head and head-hinge to coalesce into a 3D honeycomb network with greater fractal dimension, less lacunarity, smaller water hole diameter and more water holes. This increased the capillary pressure experienced by the bound water, causing immobile water to migrate towards the bound water. The present study may be necessary to improve the mechanism of water migration in protein gel systems and to promote the industrial application of high pressure processing technology in surimi-based foods.


Assuntos
Temperatura Alta , Água , Animais , Peixes/metabolismo , Miosinas/metabolismo , Géis/química , Produtos Pesqueiros/análise
6.
Environ Sci Pollut Res Int ; 30(34): 82286-82296, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37326741

RESUMO

This study examines how financial technology (FinTech) and green bonds have affected the ability of firms to finance energy efficiency measures by using data obtained from a subset of Chinese companies listed on the A-share market between 2011 and 2021. We apply the quantile-on-quantile method, which allows us to examine the interdependence of time series in each economy separately and yields data on the global and national levels indicating the relationship between the variables. The results show that an increase in both direct and indirect financing for businesses, as well as inter-bank competition, can greatly mitigate the financial limitations that firms suffer as a result of FinTech expansion. Our estimates show that the energy efficiency of the countries we chose improves when they are financed with green bonds across all quantiles of the data. Organizations not owned by the state, SMBs, and the more rapidly developing eastern half of China promise to benefit the most from the moderating effect of FinTech because of the faster pace of development there. The immediate ameliorating effect that financial technology has on reduced lending criteria mostly benefits businesses with either a strong innovation rate or a poor social responsibility performance rate. This is because businesses sharing either of these features are more likely to experiment and develop new products. Both theoretical and practical repercussions of this finding are explored.


Assuntos
Investimentos em Saúde , Desenvolvimento Sustentável , China , Comércio/economia , Investimentos em Saúde/economia , Responsabilidade Social , Desenvolvimento Sustentável/economia , Tecnologia Digital/economia , Conta Bancária
7.
Financ Res Lett ; : 103899, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37360750

RESUMO

Our paper studies the impact of the COVID-19 epidemic on commodity pricing premiums in the Chinese commodity futures market. After summarizing the explanatory power of documented benchmark pricing factors, we apply the difference-in-difference regression for our event study. We document a substantial impact of the COVID-19 pandemic on increasing the commodity basis premium by at least 30%. Basis-momentum premium, especially for agriculture futures, also increases during the epidemic. The results are robust and validated by sub-sample regressions. The influence of COVID-19 on the commodity market is more prevailing than the trade war.

9.
Int J Food Microbiol ; 399: 110253, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37210955

RESUMO

This study was conducted to compare the effects of ultraviolet light (UV), chemical sanitizers, and heat treatments on Salmonella inactivation and preservation of almond quality. Whole, skinless, and sliced almonds, representing different shape and surface topography, were inoculated with a Salmonella cocktail consisting of S. Montevideo, S. Newport, S. Typhimurium, S. Heidelberg, and S. Enteritidis. Inoculated almonds (50 g) were treated by UV (30 mW/cm2, 30 or 60 min), 75 °C heat (up to 150 min), and chemical sanitizers (3 % hydrogen peroxide (H2O2) and 1 % cetylpyridinium chloride (CPC), 30 or 60 min) alone or in combinations. Uninoculated almonds were similarly treated for analyzing color, visual appearance, and weight changes. In general, UV treatment alone was ineffective in inactivating Salmonella; the 30- and 60-min UV treatments reduced Salmonella by 1.3 (± 0.1) and 1.7 (± 0.1), 2.7 (± 0.2) and 3.3 (± 0.1), and 1.3 (± 0.1) and 1.7 (± 0.1) log CFU/g on whole, skinless, and sliced almonds, respectively. Prior wetting of almonds with water and chemical solutions in a few cases significantly (P < 0.05) increased the UV inactivation of Salmonella. The most pronounced Salmonella killing effect achieved by the combined treatments were: 1-min H2O2 dipping followed by 60-min UV treatment for whole (3.0 logs) and skinless almonds (3.8 logs) and 1-min CPC dipping followed by 60-min UV treatment for sliced almonds (3.0 logs). However, none of those achieved >4 log reductions of Salmonella as required by FDA. The 30-min UV treatment produced discolored but overall acceptable almonds, whereas the 60-min UV treatment led to deteriorated almonds including a dark color, oil extraction, and shrunk kernel size. Prior wetting reduced the sample weight loss but caused local burning and kernel cracking. A sequential approach of a 60-min 75 °C heat treatment and two 30-min wet UV treatments successfully reduced Salmonella by >4 logs, but more severe kernel cracking occurred. In contrast, a single heat treatment of vacuum packaged whole almonds at 75 °C for 150 min was capable of achieving >5 log reductions of Salmonella while preserving almond color and visual qualities and minimizing weight loss. These results clearly demonstrated that the heat treatment was a much better processing technology than UV and sanitizers for raw almond pasteurization.


Assuntos
Prunus dulcis , Temperatura Alta , Contagem de Colônia Microbiana , Salmonella enteritidis , Peróxido de Hidrogênio/farmacologia , Raios Ultravioleta , Microbiologia de Alimentos
10.
Food Microbiol ; 113: 104269, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37098429

RESUMO

This study investigated the effects of inoculation method, water activity (aw), packaging method, and storage temperature and duration on the survival of Salmonella on almonds as well as their resistance to subsequent thermal treatments. Whole almond kernels were inoculated with a broth-based or agar-based growth Salmonella cocktail and conditioned to aw of 0.52, 0.43 or 0.27. Inoculated almonds with aw of 0.43 were treated with a previously validated treatment (4 h of dry heat at 73 °C) to determine the potential differences in heat resistance resulted from the two inoculation methods. The inoculation method did not significantly (P > 0.05) impact the thermal resistance of Salmonella. Inoculated almonds at aw of 0.52 and 0.27 were either vacuum packaged in moisture-impermeable mylar bags or non-vacuum packaged in moisture-permeable polyethylene bags before stored at 35, 22, 4, or -18 °C for up to 28 days. At selected storage intervals, almonds were measured for aw, analyzed for Salmonella population level, and subjected to dry heat treatment at 75 °C. Over the month-long storage of almonds, Salmonella populations remained almost unchanged (<0.2 log CFU/g) at 4 °C and -18 °C and declined slightly (<0.8 log CFU/g) at 22 °C and more substantially (1.6-2.0 log CFU/g) at 35 °C regardless of the inoculation method, packaging method, and almond aw. When stored at 35 °C, almonds with initial aw of 0.52 had significantly higher (P < 0.05) Salmonella reductions than those with initial aw of 0.27. Prior storage of almonds vacuum packaged in mylar bags at temperatures between -18 °C and 35 °C for 28 days affected their aw levels but did not significantly (P > 0.05) affect the subsequent thermal resistance of Salmonella at 75 °C regardless of almond aw and storage duration. Salmonella on almonds with higher aw was more sensitive to heat treatment than those with lower aw. To achieve >5 log CFU/g reductions of Salmonella, a dry heat treatment at 75 °C for 4 and 6 h was needed for almonds with initial aw of 0.52 and 0.27, respectively. When applying the dry heating technology for almond decontamination, the processing time needs to be determined based on initial aw of almonds regardless of storage condition or age of almonds within the current design frame.


Assuntos
Prunus dulcis , Humanos , Temperatura , Contagem de Colônia Microbiana , Viabilidade Microbiana , Água , Manipulação de Alimentos/métodos , Microbiologia de Alimentos , Salmonella , Temperatura Alta
11.
Sci Rep ; 13(1): 1191, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36681712

RESUMO

The sphere decoding (SD) algorithm can provide (sub)optimal solutions with reduced computational complexity of maximum likelihood (ML) detection for multi-input multi-output (MIMO) communication systems. In this paper, we propose a novel low complexity symmetric-coded based SD algorithm for short polar codes with low rate. At the encoding stage, the first N/2 sub-channels transmit the frozen bits, while the information bits are selected from the latter N/2 sub-channels. Two symmetric codes are generated due to the mathematical structure of the generator matrix, which is well conditioned to the SD search. At the decoding stage, the presented SD algorithm computes the Euclidean distance value by the combined signals to estimate the latter N/2 input bits. Furthermore, the backtrack operation starts from the earlier [Formula: see text]-th bit, which can significantly reduce the average visited nodes (AVN). Simulation results show that, compared to the original SD algorithm, the presented variant of the SD algorithm can reduce the AVN to [Formula: see text] for the polar code P(64, 14) at SNR = 1  dB with a performance loss within 0.2 dB. The presented SD algorithm may find applications in MIMO systems where the complexity of the standar ML detection increases exponentially with the transmitting antennas.


Assuntos
Algoritmos , Simulação por Computador
12.
Int J Food Microbiol ; 384: 109975, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36257184

RESUMO

Sprouts have been involved in many outbreaks of salmonellosis where seeds were identified as the likely source of contamination. This study aimed to develop an effective heat treatment that could achieve a >5-log reduction of Salmonella inoculated on alfalfa seeds while maintaining seed viability and vigor. Effects of seeds' water activity (aw) and heat treatment temperature on Salmonella inactivation and seed viability were determined. Alfalfa seeds were dip-inoculated with a four-strain Salmonella cocktail and dried to aw of 0.05-0.20. The inoculated seeds were then placed in sealed glass tubes and heated at 65.9, 71.0, and 76.6 °C for up to 180 h. Increasing aw of seeds greatly improved thermal inactivation of Salmonella. For example, to achieve a >5-log reduction of Salmonella on seeds, treatment times of 140 and 60 h at 71.0 °C were required for aw of 0.1 and 0.2, respectively. Treatment temperature also greatly affected inactivation of Salmonella on alfalfa seeds. For example, to achieve a >5-log reduction of Salmonella on seeds with aw of 0.2, treatment times of 180 and 60 h were required for temperatures of 65.9 and 71.0 °C, respectively. Seeds' aw was critical for preserving seed viability. When seeds were treated at 71.0 °C for 60 h, increasing aw from 0.1 to 0.2 decreased the sprout yield ratio from 103.9 % to 73.7 %. Treatment of seeds with aw of 0.1 at 71.0 °C was found to be optimum for achieving a desirable Salmonella inactivation level while maintaining seed viability, resulting in 4.2 and 6.0 log reductions of Salmonella and yield ratios of 100.7 % and 96.1 % after 100- and 140-h treatments, respectively. This optimum heat treatment was compared with the traditional 20,000-ppm chlorine wash in terms of Salmonella inactivation and preservation of seed viability and found to be a far superior disinfection method. The chlorine treatment achieved 1.8 and 2.0 log reductions of Salmonella and yield ratios of 70.9 % and 65.1 % after 15- and 20-min treatments, respectively.


Assuntos
Medicago sativa , Água , Temperatura , Água/farmacologia , Cloro/farmacologia , Calefação , Contagem de Colônia Microbiana , Salmonella , Sementes , Microbiologia de Alimentos
13.
Molecules ; 27(24)2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36557856

RESUMO

Harvesting seasons are crucial for the physicochemical qualities of large-leaf-variety black tea. To investigate the effect of harvesting seasons on physicochemical qualities, the color and sensory characteristics of black tea produced from "Yinghong 9" (Yh) and its mutant "Huangyu" (Hy) leaves were analyzed. The results demonstrated that Hy had better chemical qualities and sensory characteristics, on average, such as a higher content of tea polyphenols, free amino acids, caffeine, galloylated catechins (GaCs) and non-galloylated catechins (NGaCs), while the hue of the tea brew (ΔE*ab and Δb*) increased, which meant that the tea brew was yellower and redder. Moreover, the data showed that the physicochemical qualities of SpHy (Hy processed in spring) were superior to those of SuHy (Hy processed in summer) and AuHy (Hy processed in autumn), and 92.6% of the total variance in PCA score plots effectively explained the separation of the physicochemical qualities of Yh and Hy processed in different harvesting seasons. In summary, Hy processed in spring was superior in its physicochemical qualities. The current results will provide scientific guidance for the production of high-quality large-leaf-variety black tea in South China.


Assuntos
Camellia sinensis , Catequina , Cafeína/análise , Camellia sinensis/química , Catequina/química , Folhas de Planta/química , Estações do Ano , Chá/química
14.
J Exp Clin Cancer Res ; 41(1): 330, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36419136

RESUMO

BACKGROUND: Glycolysis metabolism is an attractive target for cancer therapy. Reprogramming metabolic pathways could improve the ability of metabolic inhibitors to suppress cancers with limited treatment options. The ubiquitin-proteasome system facilitates the turnover of most intracellular proteins with E3 ligase conferring the target selection and specificity. Ubiquitin protein ligase E3 component N-recognin 7 (UBR7), among the least studied E3 ligases, recognizes its substrate through a plant homeodomain (PHD) finger. Here, we bring into focus on its suppressive role in glycolysis and HCC tumorigenesis, dependent on its E3 ubiquitin ligase activity toward monoubiquitination of histone H2B at lysine 120 (H2BK120ub). METHODS: In this study, we carried out high-throughput RNAi screening to identify epigenetic candidates in regulating lactic acid and investigated its possible roles in HCC progression. RESULTS: UBR7 loss promotes HCC tumorigenesis both in vitro and in vivo. UBR7 inhibits glycolysis by indirectly suppressing HK2 expression, a downstream target of Nrf2/Bach1 axis. Mechanically, UBR7 regulates H2BK120ub to bind to Keap1 promoter through H2BK120ub monoubiquitination, thereby modulating Keap1 expression and downstream Nrf2/Bach1/HK2 signaling. Pharmaceutical and genetic inhibition of glycolytic enzymes attenuate the promoting effect of UBR7 deficiency on tumor growth. In addition, methyltransferase ALKBH5, downregulated in HCC, regulated UBR7 expression in an m6A-dependent manner. CONCLUSIONS: These results collectively establish UBR7 as a critical negative regulator of aerobic glycolysis and HCC tumorigenesis through regulation of the Keap1/Nrf2/Bach1/HK2 axis, providing a potential clinical and therapeutic target for the HCC treatment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Carcinogênese/genética , Glicólise , Transformação Celular Neoplásica , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo
15.
Cell Death Discov ; 8(1): 449, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36344496

RESUMO

Accumulating evidence suggests that long noncoding RNAs (lncRNAs) are deregulated in hepatocellular carcinoma (HCC) and play a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the current understanding of the role of lncRNAs in NAFLD-associated HCC is limited. In this study, transcriptomic profiling analysis of three paired human liver samples from patients with NAFLD-driven HCC and adjacent samples showed that LINC01468 expression was significantly upregulated. In vitro and in vivo gain- and loss-of-function experiments showed that LINC01468 promotes the proliferation of HCC cells through lipogenesis. Mechanistically, LINC01468 binds SHIP2 and promotes cullin 4 A (CUL4A)-linked ubiquitin degradation, thereby activating the PI3K/AKT/mTOR signaling pathway, resulting in the promotion of de novo lipid biosynthesis and HCC progression. Importantly, the SHIP2 inhibitor reversed the sorafenib resistance induced by LINC01468 overexpression. Moreover, ALKBH5-mediated N6-methyladenosine (m6A) modification led to stabilization and upregulation of LINC01468 RNA. Taken together, the findings indicated a novel mechanism by which LINC01468-mediated lipogenesis promotes HCC progression through CUL4A-linked degradation of SHIP2. LINC01468 acts as a driver of HCC progression from NAFLD, highlights the potential of the LINC01468-SHIP2 axis as a therapeutic target for HCC.

16.
Cell Biosci ; 12(1): 183, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36371321

RESUMO

BACKGROUND: Exploiting cancer metabolism during nutrient availability holds immense potential for the clinical and therapeutic benefits of hepatocellular carcinoma (HCC) patients. Dietary methionine is a metabolic dependence of cancer development, but how the signal transduction integrates methionine status to achieve the physiological demand of cancer cells remains unknown. METHODS: Low or high levels of dietary methionine was fed to mouse models with patient-derived xenograft or diethyl-nitrosamine induced liver cancer. RNA sequence and metabolomics were performed to reveal the profound effect of methionine restriction on gene expression and metabolite changes. Immunostaining, sphere formation assays, in vivo tumourigenicity, migration and self-renewal ability were conducted to demonstrate the efficacy of methionine restriction and sorafenib. RESULTS: We discovered that mTORC1-c-Myc-SIRT4 axis was abnormally regulated in a methionine-dependent manner and affected the HCC progression. c-Myc rewires methionine metabolism through TRIM32 mediated degradation of SIRT4, which regulates MAT2A activity by ADP-ribosylation on amino acid residue glutamic acid 111. MAT2A is a key enzyme to generate S-adenosylmethionine (SAM). Loss of SIRT4 activates MAT2A, thereby increasing SAM level and dynamically regulating gene expression, which triggers the high proliferation rate of tumour cells. SIRT4 exerts its tumour suppressive function with targeted therapy (sorafenib) by affecting methionine, redox and nucleotide metabolism. CONCLUSIONS: These findings establish a novel characterization of the signaling transduction and the metabolic consequences of dietary methionine restriction in malignant liver tissue of mice. mTORC1, c-Myc, SIRT4 and ADP ribosylation site of MAT2A are promising clinical and therapeutic targets for the HCC treatment.

17.
Int J Mol Sci ; 23(19)2022 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-36232998

RESUMO

Liver fibrosis is a wound-healing response caused by the abnormal accumulation of extracellular matrix, which is produced by activated hepatic stellate cells (HSCs). Most studies have focused on the activated HSCs themselves in liver fibrosis, and whether hepatocytes can modulate the process of fibrosis is still unclear. Sma mothers against decapentaplegic homologue 4 (Smad4) is a key intracellular transcription mediator of transforming growth factor-ß (TGF-ß) during the development and progression of liver fibrosis. However, the role of hepatocyte Smad4 in the development of fibrosis is poorly elucidated. Here, to explore the functional role of hepatocyte Smad4 and the molecular mechanism in liver fibrosis, a CCl4-induced liver fibrosis model was established in mice with hepatocyte-specific Smad4 deletion (Smad4Δhep). We found that hepatocyte-specific Smad4 deficiency reduced liver inflammation and fibrosis, alleviated epithelial-mesenchymal transition, and inhibited hepatocyte proliferation and migration. Molecularly, Smad4 deletion in hepatocytes suppressed the expression of inhibitor of differentiation 1 (ID1) and the secretion of connective tissue growth factor (CTGF) of hepatocytes, which subsequently activated the p38 and p65 signaling pathways of HSCs in an epidermal growth factor receptor-dependent manner. Taken together, our results clearly demonstrate that the Smad4 expression in hepatocytes plays an important role in promoting liver fibrosis and could therefore be a promising target for future anti-fibrotic therapy.


Assuntos
Hepatócitos , Cirrose Hepática , Proteína Smad4 , Animais , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Receptores ErbB/metabolismo , Células Estreladas do Fígado/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Cirrose Hepática/metabolismo , Camundongos , Proteína Smad4/metabolismo , Fator de Crescimento Transformador beta/metabolismo
18.
FEBS Open Bio ; 12(11): 2025-2041, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36062301

RESUMO

Aberrant expression of members of the proteasome subunit beta (PSMB) family (including PSMB2, PSMB4, PSMB7 and PSMB8) has been reported in hepatocellular carcinoma (HCC). However the role of PSMB5 in HCC is unclear. To address this issue, we examined the expression of PSMB5 in HCC tissues using the The Cancer Genome Atlas, International Cancer Genome Consortium and Gene Expression Omnibus databases. A quantitative real-time PCR and immunohistochemistry were performed to validate the expression of PSMB5 in HCC. The survival mutation status and immune cell infiltration of PSMB5 were also evaluated in HCC. We then examined the effect of knocking down PSMB5 expression through RNA interference in the HCC cell line Huh7. High expression of PSMB5 was observed in HCC tissues and was associated with poor prognosis. PSMB5 expression and clinical characteristics were then incorporated to build a prognostic nomogram. We observed that PSMB5 expression was closely related to the abundance of B cells, CD4+ T cells, CD8+ T cells, dendritic cell macrophages and neutrophils. Moreover silencing of PSMB5 in Huh7 significantly suppressed cell proliferation and migration at the same time as increasing apoptosis. Inhibition of the phosphatidylinositol-3-kinase/Akt/mechanistic target of rapamycin pathway was observed after PSMB5 downregulation in Huh7 cells. Our findings suggest that PSMB5 may promote the proliferation of HCC cells by inactivating the phosphatidylinositol-3-kinase/Akt/mechanistic target of rapamycin signaling pathway and thus PSMB5 may have potential as a biomarker for diagnosis and prognosis of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linfócitos T CD8-Positivos , Linhagem Celular Tumoral , Proliferação de Células/genética , Sirolimo , Fosfatidilinositóis , Complexo de Endopeptidases do Proteassoma/genética
19.
Int J Food Microbiol ; 379: 109849, 2022 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-35926399

RESUMO

The goal of this study was to develop dry heat processing conditions that could achieve a >5-log reduction of Salmonella with minimal negative impact on almond quality. The effects of almond's water activity (aw) levels and packaging methods on Salmonella inactivation by dry heat were determined. Almonds were dip-inoculated in a four-strain Salmonella cocktail and conditioned to aw of 0.43, 0.33, 0.23, and 0.20. The inoculated almonds were then placed in vacuum-sealed mylar bags (vacuum packaging), ambient-sealed glass tubes (non-vacuum packaging), and petri dishes without covers (no packaging). The packaged and un-packaged almonds were treated by dry heat with 13 % relative humidity at 73 °C. Vacuum packaging in general achieved slightly better (in some cases significantly better (p < 0.05)) or similar inactivation effect on Salmonella than non-vacuum packaging. Both vacuum and non-vacuum packaging methods achieved much greater Salmonella inactivation than the no packaging method. For example, a 4-h treatment at 73 °C reduced Salmonella on almonds with aw of 0.43 by 5.1-, 4.4-, and 1.3-log for mylar bag, tube, and petri dish, respectively. Higher aw levels resulted in better inactivation of Salmonella. To achieve a >4-log reduction of Salmonella on almonds packaged in mylar bags, 3-, 6-, 8-, and 8-h of heat treatment were needed for almonds with aw values of 0.43, 0.33, 0.23 and 0.20, respectively. Vacuum packaging in combination with a 4-h heat treatment of almonds with initial aw of 0.43 or 8-h heat treatment of almonds with initial aw of 0.33 could achieved a ≥5-log reduction of Salmonella. Those two combinations resulted in very little weight loss (≤0.05 %), insignificant color change (∆E ≤ 1.26), and unnoticeable change in visual appearance of almonds, demonstrating that they could be potentially used for raw almond pasteurization.


Assuntos
Prunus dulcis , Contagem de Colônia Microbiana , Descontaminação , Microbiologia de Alimentos , Temperatura Alta , Salmonella
20.
Food Res Int ; 157: 111230, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35761546

RESUMO

The effect of optimal low-level pressure coupled with heat treatment (OPH treatment) on the gel properties and water migration of Nemipterus virgatus surimi was studied and compared with optimal high-pressure processing treatment (OP treatment) and traditional two-stage heat treatment (H treatment). Furthermore, the mechanism of OPH treatment in improving the gel properties were explored based on myosin. OPH treatment was found to be more conducive in improving the gel strength and water-holding capacity (WHC) of surimi gel than H or OP treatments. Moreover, OPH treatment induced an increase in the proportion of myosin ß-sheets and exposed more intramolecular Tyr residues as compared to the other two treatments, which promoted myosin to form large protein clusters through disulfide bonds and hydrophobic interactions, and a honeycomb three-dimensional network structure with larger fractal dimension, lower porosity, smaller water hole diameter, and a greater number of water holes, was obtained. These helped the OPH-induced surimi gel lock in more unfrozen bound water and immobile water, and ultimately rendered better gel properties.


Assuntos
Produtos Pesqueiros , Água , Animais , Produtos Pesqueiros/análise , Peixes , Géis/química , Temperatura Alta , Miosinas/química
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